Neuroblastoma is a malignant cancer of the postganglionic sympathetic nervous system that commonly presents in childhood and is derived from the neural crest cells during embryonic development. Initially it develops in the adrenal gland and metastasizes to liver, bone, bone marrow, lymph nodes, neck and chest. It is the most common cancer in babies younger than one and the second most common tumor in children. In the United State, approximately 700 children are diagnosed with neuroblastoma each year. It accounts for 7% of all childhood cancers, and is responsible for 15% of all cancer deaths in children younger than 15 years. Despite standard therapy for advanced disease including chemotherapy, surgery, and radiation, the mortality rate remains high for these patients. The five-year survival rate for children with low-risk neuroblastoma is higher than 95%, and for children with intermediate-risk neuroblastoma the survival rate is 80% to 90%, but only about 30% to 50% of children with high-risk neuroblastoma experience long-term survival.
Neuroblastoma tumor comprises populations of various heterogeneous cells including N-type cells (neuroblastic), S-type cells (substrate adherent) and I-type cells (intermediate). These cells differ at morphological and biochemical levels. N-type cells are neuroblastic with a small, rounded, loosely adherent cell body and numerous neurite-like processes. S-type cells are highly substrate adherent with a larger, flattened epithelial-like cell body. I-type cells represent a cellular intermediate in the N-type and S-type cell transdifferentiation process. At biochemical levels, S-type cells do not exhibit neuronal properties such as neurotransmitter biosynthetic enzyme activities, catecholamine uptake, or receptor proteins as do N-type cells. N-type and I-type cells express neurofilament proteins while I-type and S-type cells are more strongly positive for vimentin than N-type cells.
The most common cytogenetic features identified in low to advance stages of neuroblastoma include genomic amplification of MYCN gene, rearrangement or deletion of distal region of the chromosome 1 (1p31-arm), or alterations in chromosomes 11, 14 and 17. Mutations in tumor suppresser genes, i.e., p53, retinoblastoma, RET, p16, p18 or p27 have been reported as promoting tumerogenesis. These karyotype and cytogenetic alterations develop drug resistance and protect tumors against the available chemotherapies. For example, retinoic acid induces neuronal differentiation in neuroblastoma cells and is commonly used in residual therapy. However, neuroblastoma cells with MYCN-amplified oncogene do not respond to retinoic acid.
Sparstolonin B (SsnB) has been isolated from the tubers of an aquatic herb, Sparganium stoloniferum. SsnB has been shown to act as antagonist to Toll-like Receptors 2 and 4 (TLR2 and TLR4), and can exhibit anti-inflammatory properties by selectively inhibiting TLR2 and TLR4-triggered inflammatory response in mouse and human macrophages. In traditional Chinese medicine, the tubers of this herb have been used for the treatment of several inflammatory diseases. In addition, the crude extract prepared form this herb can have anti-spasmodic and certain anti-tumor properties.
What is needed in the art are targeted agents and combination chemotherapy in the treatment of neuroblastoma tumors.